It is common knowledge: As women get older, pregnancy becomes a riskier enterprise. Advanced maternal age is linked to a number of developmental disorders in children, such as Down's syndrome. Now, a study has confirmed that older mothers are more likely to give birth to a child with autism, too.

The authors of the epidemiological study, published February 8 in Autism Research, examined the parental age of more than 12,000 children with autism and nearly five million "control" children between 1990 and 1999, all living in California. The researchers found that mothers over 40 had a 51 percent higher risk of having a child with autism than mothers 25 to 29, and a 77 percent higher risk than mothers under 25.

Autism—a developmental disorder characterized by impaired social interaction and communication—appears to be on the rise. The U.S. Centers for Disease Control and Prevention now estimates that as many as one in 110 children in the U.S. has an autistic spectrum disorder—a group of developmental disorders including autism, Asperger's syndrome and pervasive developmental disorder. The prevalence of autistic spectrum disorders in California in 2007 was 12 times that from 1987, representing an average annual growth of 13 percent, according to a report from the California Department of Developmental Services. Only a fraction of these extra cases can be explained by changes to diagnostic criteria and earlier diagnoses.

Maternal age is also increasing in the U.S. A California-based study reported a three-fold increase in the number of births to women aged 40 to 44 between 1982 and 2004. But this trend toward delayed childbearing accounted for less than 5 percent of the total increase in autism diagnoses in California over the decade, according to the study—a finding that surprised Janie Shelton, a doctoral student in University of California, Davis's Department of Public Health Sciences and the study's lead author. "I would have expected to see more of a contribution, because age is a risk factor and women are having kids later," she says.

Earlier work had suggested that both maternal and paternal ages are independently associated with autism risk. But the current study found that paternal age is only a risk factor when the mother is under 30. It follows similar results obtained from the same California sample, published in September 2009 in the American Journal of Public Health, which showed that pooling data artificially inflates the risk of paternal age, and that advanced maternal age likely poses the greater risk. "It's nice to see replication of prior work," says Peter Bearman, co-author of the 2009 paper. Neither research team investigated whether increasing maternal age worsened autistic symptoms, although a 2007 study published in the Journal of Autism and Development Disorders that measured autistic children's cognitive and social function failed to make that link.

Mothers over 35 are at a higher risk for prolonged labor, premature or breeched deliveries, and birth to babies with low Apgar scores (a rating index used to evaluate the condition of a newborn infant)—all factors that have been associated with autism. But they might also be more likely to seek diagnoses to explain their child's abnormal behavior. "That's definitely an important thought, and I think that there is some evidence to suggest that people with higher education and higher socioeconomic status in general are more adept at navigating the diagnostic process here in California," Shelton says. "[Parents] need to be motivated to get the diagnostic and treatment services that are granted to them by the state. There are certain cases we're missing because the parents don't know about the services that are available or they haven't worked out how to navigate the system yet." The proportion of parents of autistic children with fewer than 24 years of combined education in the study was smaller than that of "control" birth parents, (19 percent and 36 percent, respectively).

Other contributors to the increasing incidence of autism remain unclear. "We're doing a lot of research into environmental risk factors," Shelton says, describing ongoing research into possible nutritional factors and toxic chemical exposure during labor and development. It is possible that the increased risk associated with maternal age might reflect the mother's longer cumulative exposure to unknown environmental factors, the authors report.

The research team published an earlier report in the same journal describing high-incidence geographic clusters in California, another finding in line with Bearman's work that suggests environmental processes and social influences (why someone would live in a particular neighborhood) might be contributing factors. Maternalautoimmunity is another theory proposed by the researchers, who previously reported that some mothers of autistic children had antibodies to fetal brain proteins in their plasma. These antibodies (which might increase in number with age) could transfer into the fetus and interfere with early brain development, the researchers report.

Whereas biomedical studies are required to uncover the mechanisms underlying the disorder, Shelton says the present epidemiological study was important in clarifying the nuanced relationship between maternal age and autism, and defining its contribution to the rise in cases. It might have even provided biological clues. "It really is a maternally mediated biological process that's going on," Shelton says.

Although it is rising, the risk of autism is still very low and shouldn't affect the decision to have children at any age, Shelton says. "People should pursue their families whenever it's right for them," she says, adding that soon-to-be parents should "just stay as healthy as possible," and steer clear of dangerous exposures. She also encourages parents with autistic children to get involved in research. "I think parents are anxious because science hasn't figured it out yet. If they have the opportunity to be involved in supporting science and autism research, that's a great thing."